Induction of amphotericin B resistance in susceptible Candida auris by extracellular vesicles

Drug resistance derived from extracellular vesicles (EVs) is an increasingly important research area but has seldom been described regarding fungal pathogens. Here, we characterized EVs derived from a triazole-resistant but amphotericin B-susceptible strain of Candida auris. Nano- to microgram conce...

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Veröffentlicht in:Emerging microbes & infections 2022-12, Vol.11 (1), p.1900-1909
Hauptverfasser: Chan, Walton, Chow, Franklin Wang-Ngai, Tsang, Chi-Ching, Liu, Xueyan, Yao, Weiming, Chan, Tony Tat-Yin, Siu, Gilman Kit-Hang, Ho, Alex Yat-Man, Luk, Kristine Shik, Lau, Susanna Kar-Pui, Woo, Patrick Chiu-Yat
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container_end_page 1909
container_issue 1
container_start_page 1900
container_title Emerging microbes & infections
container_volume 11
creator Chan, Walton
Chow, Franklin Wang-Ngai
Tsang, Chi-Ching
Liu, Xueyan
Yao, Weiming
Chan, Tony Tat-Yin
Siu, Gilman Kit-Hang
Ho, Alex Yat-Man
Luk, Kristine Shik
Lau, Susanna Kar-Pui
Woo, Patrick Chiu-Yat
description Drug resistance derived from extracellular vesicles (EVs) is an increasingly important research area but has seldom been described regarding fungal pathogens. Here, we characterized EVs derived from a triazole-resistant but amphotericin B-susceptible strain of Candida auris. Nano- to microgram concentrations of C. auris EVs prepared from both broth and solid agar cultures could robustly increase the yeast's survival against both pure and clinical amphotericin B formulations in a dose-dependent manner, resulting in up to 16-fold changes of minimum inhibitory concentration. Meanwhile, this effect was not observed upon addition of these EVs to C. albicans, nor upon addition of C. albicans EVs to C. auris. No change in susceptibilities was observed upon EV treatment for fluconazole, voriconazole, micafungin, and flucytosine. Mass spectrometry indicated the presence of immunogenic-/drug resistance-implicated proteins in C. auris EVs, including alcohol dehydrogenase 1 as well as C. albicans Mp65-like and Xog1-like proteins in high quantities. Based on these observations, we propose a potential species-specific role for EVs in amphotericin B resistance in C. auris. These observations may provide critical insights into treatment of multidrug-resistant C. auris.
doi_str_mv 10.1080/22221751.2022.2098058
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subjects amphotericin B
Antifungal agents
Candida auris
Drug dosages
Drug resistance
Epidemics
Extracellular vesicles
Fungal infections
Hospitals
Life sciences
Medicine
solid media EV purification
title Induction of amphotericin B resistance in susceptible Candida auris by extracellular vesicles
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